Two areas of metabolic regulation are under continuing inquiry: 1) Phosphorus metabolism in pancreatic islets is being evaluated to define its role in stimulus-secretion coupling for insulin. A new method to assess phosphate influx and efflux concurrently, is being developed. It will be applied to determine whether the processes are mediated separately and to elucidate underlying determinants. Factors delimiting the turnover of islet phosphatidylinositol are being ascertained. New techniques involving equilibrium labeling during tissue culture are being established to permit microchemical assays of regulatoryorganophosphates in islets. These approaches are being correlated with estimate of ion fluxes (Ca++, Rb+, Cl-, and Arsenate) to characterize islets with physiological impairments in their responsiveness to nutrient secretagogues for insulin i.e. i) islets from fetal rats; and ii) islets from adult rats with induced "starvation diabetes" due to deprivation of glucose during tissue culture. 2) Selected aspects of Intermediary Metabolism in Pregnancy are being examined to determine the influence of maternal fuels upon development of the conceptus. The changes in maternal metabolism during the first 6-8 weeks of pregnancy are being studied and some of the fuel mixtures that obtain at this time are being tested for their teratogenic potentialities in orfan culture of rat embryos. Alterations in maternal metabolism during the transition from early to mid-gestation are being defined to identify factors evoking insulin resistance and "triggering" gestational diabetes. Possible impacts of maternal fuels upon developing fetal cells during the last half of gestation are being evaluated in model systems: i) the effects of maternal amino acids upon the maturation of neurotransmitter biosynthesis in rat brain are under investigation; and ii) the effects of ambient fuels upon biochemical and functional maturation of B cells of cultured fetal islets are also being ascertained. The efforts with brain and islets are addressed tothe proposition that "behavioral", "anthropometric", and "metabolic" teratogenesis may be elicited by the action of aberrant fuel mixtures of maternal origin upon certain terminally-differentiating fetal cells during gestation.